Acute retinal necrosis
Acute retinal necrosis (ARN) falls within the realm of necrotizing retinitis; it is an inflammatory condition that primarily affects the posterior pole. It typically features posterior uveitis and retinitis, inflammatory conditions believed to be caused by viruses within the herpes family. The principal viral agents are believed to be Varicella Zoster Virus (VZV) as well as Herpes Simplex Virus (HSV-1 and HSV-2), and, in much rarer cases, Cytomegalovirus (CMV) and Epstein Barr Virus (EBV).
ARN was initially described by Urayama and colleagues in Japan in 1971.
ARN is believed to result from the combination of retinal infiltration and occlusive arteriolitis in the setting of, most commonly, HSV or VZV infection. Serious visual loss may occur as a result of later retinal detachment or, much more rarely, optic neuropathy.
Genetics may play some role in an individual’s risk for ARN:
HLA-DQw7, HLA-Bw62, and HLA-DR4 in American Caucasians
HLA-Aw33, HLA-B44, and HLA-DRw6 in Japanese population
This clinical entity is uncommon in the pediatric population but rather tends to affect adults in their fifth to seventh decades. A clear gender predilection has not been consistently demonstrated. Unlike other forms of infectious retinitis, immunocompetent patients tend to be more affected than immunosuppressed patients.
There appear to be two distinct disease phases:
(1) acute herpetic phase, in which inflammation of the retina, retinal arteries, and choroidal vasculature occurs
(2) late cicatricial phase, in which retinal holes and tears commonly leading to subsequent retinal detachment occur
Acute phase: Viral particles in the retina and the vitreous provoke an intense inflammatory response. Retinal opacification corresponds with infiltration of the retina with viral particles and mononuclear cells. Lymphocytes and plasma cells, which produce antibodies to the provocative viral agent, likewise permeate the vitreous. Additionally, characteristic inflammation of the retinal arterioles occurs, resulting in vaso-occlusion and necrosis of dependent, downstream retinal tissue. Choroidal vasculature may also be beset by similar inflammatory changes.
Cicatricial phase: Organizational changes in the vitreous are thought to be the result of previous cellular infiltration during the acute phase. Contractile membranes may form in the vitreous and on the surface of the thinned, necrotic retina. Approximately 50% of patients will develop retinal detachments in the affected eye after ARN; the majority of retinal detachments occur within 3 months of the onset of ARN.
The use of antiviral agents reduces the duration of the active phase of ARN and may thereby potentially minimize the duration and extent of retinal necrosis. Chronic use of antivirals after resolution of the active phase of ARN in one eye has also been shown to reduce the incidence of ARN in the fellow eye.
Prevention of the late visual sequelae of acute retinal necrosis, namely that of retinal detachment, may be partially reduced through prophylactic laser photocoagulation of the retina.
Viral particles were originally identified, using electron microscopy, in the retina of those enucleated eyes with ARN.
Signs and symptoms
Patients with ARN typically present with acute onset of vision loss in one eye, which may be associated with redness, photophobia, pain, floaters, and flashes. Two-thirds of cases present with unilateral involvement.
Anterior segment involvement may include episcleritis, scleritis, corneal edema, keratic precipitates, and anterior chamber inflammation. Classically, posterior segment involvement includes vitreous inflammation, retinal vascular arteriolitis, and peripheral retinitis. Retinitis typically begins as multifocal areas of retinal yellowing and opacification, oftentimes with scalloped edges; initially, this patchy retinitis usually appears peripherally and, with progression, becomes increasing confluent and more posterior in its location.
The American Uveitis Society established the following as diagnostic criteria: (1) One or more foci of retinal necrosis with discrete borders, located in the peripheral retina (2) Rapid progression in absence of antiviral therapy (3) Circumferential spread (4) Occlusive vasculopathy, affecting arterioles (5) Prominent vitritis and/or anterior chamber inflammation
The diagnosis of ARN is usually made based upon clinical characteristics. However, in certain cases, it may be appropriate to analyze an aqueous or vitreous sample. In very rare examples, diagnostic vitrectomy or endoretinal biopsy may be necessary.
The following tests may be performed on aqueous or vitreous samples for further diagnostic certainty:
-use of direct or indirect immunofluorescence to identify viral antigens
-measurement of viral antibodies
-intraocular antibody titers with calculation of the Goldmann-Witmer coefficient
Serologic testing may also aid in diagnosis.
Progressive outer retinal necrosis (PORN)
Without intervention, the active phase of the disease can last between 6-12 weeks, while treatment with antivirals and/or steroids may reduce the latency to 4-6 weeks. Treatment modalities may include antiviral, anti-inflammatory, and antithrombotic therapy as well as retinal detachment prophylaxis.
Antiviral therapy can be administered systemically (intravenously or by mouth) as well as through intravitreal injection. Prior to the mid-1990’s, antiviral agents were traditionally administered intravenously for at least the first week after diagnosis of ARN because it was believed that higher serum and intraocular concentrations of the antiviral agent could be achieved through IV administration; thereafter, it was considered appropriate to transition the patient to PO antivirals (acyclovir, famciclovir, valacyclovir, or valganciclovir) for an additional 4-12 weeks. Since the advent of newer antiviral agents, many physicians advocate using oral antiviralagents such as famciclovir, valacyclovir or valganciclovir as initial induction agents for treatment of ARN as well. Intravitreal delivery of antiviral agents is also used by many. Steroids and aspirin may also be appropriate for treatment.
Commonly used systemic antiviral agents include:
Antiviral agents administered intravitreally may include:
• Ganciclovir (200-2000 ug per 0.1 mL)
• Foscarnet (1.2-2.4 mg per 0.1 mL)
Steroids may have a beneficial therapeutic effects if initiated 24-48 hours after the start of IV antiviral therapy or once regression of retinal necrosis been demonstrated:
• Prednisone 0.5-2.0 mg/kg/day by mouth for up to 6-8 weeks
Aspirin may minimize vascular thrombosis and propagation of further retinal ischemia and necrosis.
Topical steroid drops have also been shown to be beneficial, depending upon the degree of anterior segment inflammation.
Topical antiviral therapy has been shown not to be efficacious in treatment of ARN.
Patients with unilateral ARN should be closely followed with dilated examination of both of their eyes. Approximately 50% of patients with ARN will go on to develop a retinal detachment. Reports of second eye involvement range from 3-35%, with variable involvement attributable to etiologic agent, course of therapy, and immune status.
Some retina specialists advocate the use of prophylactic laser along the posterior margin of the junction of necrotic and non-necrotic retina to prevent incidence of retinal detachment. The rates of success in preventing retinal detachment are variable, and consensus does not exist on whether laser demarcation should be employed.
Vitrectomy with or without use of scleral buckle, with use of either gas or silicone oil, is reserved for those cases in which retinal detachment occurs.
Retinal holes and tears
The visual outcome on those eyes affected by ARN is variable and largely depends upon vision at time of presentatation as well as whether or not a retinal detachment occurs secondarily. Whether or not a retinal detachment occurs may, in turn, depend upon the extent of retinal necrosis on diagnosis, the amount of vitritis overlying areas of retinal necrosis (with more vitritis associated with a higher risk of RD), and varying response to treatment regimens.
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